Y-L Lu1, T-T Ye, Y Chen, J Yu, L-J Zhao, N-J Wang, B-R Jiang, J Qiao, L-Z Yang. 1. Division of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China 200011. dryanginsh@yahoo.com
Abstract
AIMS: To investigate whether rosiglitazone (ROS) protects diabetic rats from destructive changes in the liver. METHODS: Twenty-four Sprague Dawley rats were randomly divided into 3 groups: control (NC) group (no.=8), streptozocin (STZ)-treated diabetic (DM) group (no.=8), and STZ+ROStreated diabetic (RSG) group (no.=8). After 8 weeks, the liver structure was observed by light microscopy and transmission electron microscopy. Apoptosis was detected by TUNEL, and apoptosis index was calculated. The Fas ligand (FasL) mRNA expression of apoptosis-promoting gene and cyclooxygenase- 2 (COX-2) mRNA in the liver were detected by RTPCR. COX-2 protein in the liver was tested via immunohistochemical staining. RESULTS: Compared to NC group, DM group showed a visible fatty degeneration and inflammatory cell infiltration in the liver under microscopy. Obvious hepatocyte swelling with atrophic mitochondria was observed, and the central zone of cholangiole was severely outstretched. Meanwhile, in RSG group, the hepatocyte steatosis and inflammatory cell infiltration decreased, and the hepatic ultra-structure was markedly improved. Hepatocyte apoptosis (p<0.05) and the expression levels for hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), and COX-2 protein (p<0.05) were higher in DM group compared to the NC group, while the expression level of hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), COX-2 protein (p<0.05), and hepatocyte apoptosis (p<0.05) in RSG group were decreased compared to DM group. CONCLUSION: Diabetes causes severe liver injury and ROS can protect diabetic rats from liver destruction, which may be related to inhibition of the expression of COX-2 and the hepatocyte apoptosis induced by FasL gene over expression.
AIMS: To investigate whether rosiglitazone (ROS) protects diabeticrats from destructive changes in the liver. METHODS: Twenty-four Sprague Dawley rats were randomly divided into 3 groups: control (NC) group (no.=8), streptozocin (STZ)-treated diabetic (DM) group (no.=8), and STZ+ROStreated diabetic (RSG) group (no.=8). After 8 weeks, the liver structure was observed by light microscopy and transmission electron microscopy. Apoptosis was detected by TUNEL, and apoptosis index was calculated. The Fas ligand (FasL) mRNA expression of apoptosis-promoting gene and cyclooxygenase- 2 (COX-2) mRNA in the liver were detected by RTPCR. COX-2 protein in the liver was tested via immunohistochemical staining. RESULTS: Compared to NC group, DM group showed a visible fatty degeneration and inflammatory cell infiltration in the liver under microscopy. Obvious hepatocyte swelling with atrophic mitochondria was observed, and the central zone of cholangiole was severely outstretched. Meanwhile, in RSG group, the hepatocyte steatosis and inflammatory cell infiltration decreased, and the hepatic ultra-structure was markedly improved. Hepatocyte apoptosis (p<0.05) and the expression levels for hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), and COX-2 protein (p<0.05) were higher in DM group compared to the NC group, while the expression level of hepatic COX-2 mRNA (p<0.05), FasL mRNA (p<0.01), COX-2 protein (p<0.05), and hepatocyte apoptosis (p<0.05) in RSG group were decreased compared to DM group. CONCLUSION:Diabetes causes severe liver injury and ROS can protect diabeticrats from liver destruction, which may be related to inhibition of the expression of COX-2 and the hepatocyte apoptosis induced by FasL gene over expression.
Authors: N Kabbaj; I Errabih; M Guédira; H El Atmani; K Benabed; Z Al Hamany; M Mohammadi; A Benaïssa Journal: Ann Endocrinol (Paris) Date: 2006-06 Impact factor: 2.478
Authors: J Matsuda; K Hosoda; H Itoh; C Son; K Doi; I Hanaoka; G Inoue; H Nishimura; Y Yoshimasa; Y Yamori; H Odaka; K Nakao Journal: Diabetes Date: 1998-11 Impact factor: 9.461
Authors: Michel Komajda; John J V McMurray; Henning Beck-Nielsen; Ramon Gomis; Markolf Hanefeld; Stuart J Pocock; Paula S Curtis; Nigel P Jones; Philip D Home Journal: Eur Heart J Date: 2010-01-29 Impact factor: 29.983
Authors: Lyudmila I Rachek; Larysa V Yuzefovych; Susan P Ledoux; Neil L Julie; Glenn L Wilson Journal: Toxicol Appl Pharmacol Date: 2009-07-24 Impact factor: 4.219